Illuminating the dark side of neuraminidase in influenza immunity.

The influenza neuraminidase has historically been understudied compared to its surface protein counterpart, hemagglutinin. In two recent Immunity papers, Hansen et al. and Lei et al. bolster resurging interest in neuraminidase-targeting antibodies and their implications for therapy and "universal" vaccines.

Identification of sensitive indicators in immune response for leprosy affected patients: An observational clinical study of safety and immunogenicity of influenza vaccine.

ABSTRACT: Cured leprosy patients have special physical conditions, which could pose challenges for safety and immunogenicity after immunization. We performed an observational clinical study aimed to identify the safety and immunogenicity of influenza vaccine in cured leprosy patients. A total of 65 participants from a leprosarium were recruited into leprosy cured group or control group, and received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days proactive observation of any adverse events. Hemagglutination and hemagglutination inhibition test was performed to evaluate serum antibody titer, flow cytometry was conducted to screen of cytokines level. The total rate of reactogenicity was 0.0% [0/41] in leprosy cured group and 37.5% [9/24] in control group. The seroconversion rate for H1N1 was difference between leprosy cured group and control group (41.83% vs 79.17%, P = .0082), but not for H3N2 (34.25% vs 50.00%, P = .4468). At day 0, leprosy cured group have relatively high concentration of interleukin-6, interleukin-10, tumor necrosis factor, interferon-γ, and interleukin-17 compared to control group. The interleukin-2 concentration increased 2 weeks after vaccination compared to pre-vaccination in leprosy cured group, but declined in control group (0.92 pg/ml vs -0.02 pg/ml, P = .0147). Leprosy cured group showed a more rapid down-regulation of interleukin-6 when influenza virus was challenged compared to control group (-144.38 pg/ml vs -11.52 pg/ml, P < .0001). Subgroup analysis revealed that the immunization administration declined interleukin-17 concentration in Tuberculoid type subgroup, but not in Lepromatous type subgroup or control group. Clinically cured leprosy patients are relatively safe for influenza vaccine. Leprosy cured patient have immune deficit in producing antibody. Interleukin-6 and interleukin-17 were 2 sensitive indicators in immune response for leprosy affected patients. The identification of indicators might be help management of leprosy and used as predictive markers in leprosy early symptom monitoring.

Erythema Nodosum Leprosum Triggered by Antecedent Influenza Vaccine and Respiratory Tract Infection: A Case Report.

We present a patient with new-onset erythema nodosum leprosum months after successful treatment of her mid-borderline leprosy, which was likely triggered by a combination of antecedent influenza vaccination and upper respiratory tract infection.

The safety of influenza vaccine in clinically cured leprosy patients in China.

BACKGROUND: Leprosy is an infectious disease caused by the bacterium Mycobacterium leprae. Influenza vaccine is an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. But the safety of applying influenza vaccine on the clinical cured leprosy patients is unclear. METHODS: We conducted an observational clinical study, in Wuhan between November 15, 2016 and March 1, 2017. Two groups of participants ≥50 years of age received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days observation of any solicited and unsolicited adverse events. RESULTS: A total of 134 subjects were included in the study. The total rate of reactogenicity was 5.4% [2/37] in leprosy group and 15.5% [15/ 97] in control group, the difference of reactogenicity between two groups was not significant (p = 0.1522). For solicited injection-sites adverse events (AEs), 12.4% [12/ 97] participants in the control group reported of itching, pain, erythema, swelling or induration, and no participants in leprosy group reported of any solicited injection-sites AEs. For solicited systemic AEs, 7.2% [7 / 97] participants in the control group reported of fever, malaise or headache, and 2.7% [1 / 37] participants in the leprosy group reported of fever, statistic result showed that the difference was not significant (p = 0.4438). Unsolicited AEs was reported by one male aged 76, 4 hours after vaccination administration, his plantar ulcer area began bleeding. All AEs were grade 1 or grade 2, and no recurrence of lepra reaction, AEs leading to early withdrawal from the study, or deaths were reported in this study. CONCLUSIONS: To our knowledge, the present study is the first clinical study to evaluate the safety of influenza vaccine in clinically cured leprosy patients. We concluded that clinically cured leprosy patients are relatively safe for influenza vaccine. More importantly, our study make a positive and scientific efforts to eradicate discrimination on leprosy. In our study, we described a patient with plantar ulcer undergoing bleeding for 4 hours after vaccine administration. Based on evidence we have, we interpret that this adverse event may probably associated with vaccine, and patients with ulcer and leprosy need intensive attention after vaccines administration.

Effect of Lactobacillus paracasei subsp. paracasei, L. casei 431 on immune response to influenza vaccination and upper respiratory tract infections in healthy adult volunteers: a randomized, double-blind, placebo-controlled, parallel-group study.

BACKGROUND: Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms related to respiratory infections. OBJECTIVE: The objective of the study was to investigate the effect of the probiotic strain Lactobacillus paracasei subsp. paracasei, L. casei 431 (Chr. Hansen A/S) (hereafter, L. casei 431) on immune response to influenza vaccination and respiratory symptoms in healthy adults. DESIGN: A randomized double-blind, placebo-controlled trial was conducted in 1104 healthy subjects aged 18-60 y at 2 centers in Germany and Denmark. Subjects were randomly assigned to receive an acidified milk drink containing ≥10(9) colony-forming units of L. casei 431 (n = 553) or placebo (n = 551) for 42 d. After 21 d, subjects received the seasonal influenza vaccination. The primary outcome was seroprotection rate (anti-influenza antibody titers by hemagglutination inhibition) 21 d after vaccination. Other outcomes were seroconversion rate and mean titers, influenza A-specific antibodies and incidence, and duration and severity of upper respiratory symptoms. Antibiotic use and use of health care resources were recorded. RESULTS: There was no effect of L. casei 431 on immune responses to influenza vaccination. Generalized linear mixed modeling showed a shorter duration of upper respiratory symptoms in the probiotic group than in the placebo group (mean ± SD: 6.4 ± 6.1 vs. 7.3 ± 9.7 d, P = 0.0059) in the last 3 wk of the intervention period. No statistically significant differences were found for incidence or severity. CONCLUSIONS: Daily consumption of L. casei 431 resulted in no observable effect on the components of the immune response to influenza vaccination but reduced the duration of upper respiratory symptoms. The trial was registered at www.isrctn.com as ISRCTN08280229.

Avaliação situacional de influenza pós pandemia de 2009 - uma breve revisão / Situational assessment of influenza post 2009 Pandemic - a brief review

Os vírus influenza são responsáveis por epidemias anuais com gravidade da doença variável. Causam infecção respiratória aguda com elevada transmissibilidade devido sua alta variabilidade genética, capacidade de adaptação e rápida disseminação. Os vírus influenza apresentam genoma fragmentado,o que ocasiona variações antigênicas frequentes, e consequentemente pode induzir o aparecimento de subtipos mais virulentos, como ocorreu em 2009,quando foi registrada pandemia por um novo vírus Influenza A H1N1. A Organização Mundial de Saúde(OMS) estima que a gripe acometa 5 a 15% da população,ocasionando 3 a 5 milhões de casos graves e 250.000 a 500.000 mortes anualmente. As epidemias anuais de gripe e o risco de novas pandemias tornamo monitoramento epidemiológico do vírus influenza fundamental e, para isto, a OMS coordena a Rede Mundial de Vigilância da Influenza com a finalidade de fornecer informações necessárias para a escolha das variantes virais que farão parte da composição anual da vacina, visto que a vacinação é uma das medidas mais efetivas para prevenção da gripe e suas complicações. Além disso, a rede constitui uma vigilância rápida para identificações de vírus influenza emergentes com potencial epidêmico ou pandêmico.Esta vigilância é viabilizada pelos resultados dos testes laboratoriais que são ferramentas importantes para a Saúde Pública, sendo fundamentais para a contenção e prevenção dos vírus circulantes. O objetivo deste estudo foi apresentar informações relacionadas ao vírus influenza e a doença, como são realizados o diagnóstico e monitoramento pelas redes de vigilâncias mundiais pós-pandemia e, ainda, quais os novos desafios que se apresentam.

Influenza viruses are responsible for annual epidemics with patients presenting variable degrees of diseases everity. These virus can cause acute respiratory infection with a high transmissibility due to its high genetic variability, adaptability and rapid spread. Influenza viruses have fragmented genome which causes frequent antigenic variation, which can result in more virulent subtypes emergence, as occurred in 2009 when it was described a new pandemic influenza virus H1N1. WHO estimates that flu affects 5-15% of the population and it causes 3 to 5 million of severe cases and 250.000 to 500.000 deaths annually. The annual influenza epidemics and the new pandemics risk high lights the importance of Influenza virus epidemiological monitoring. Based in this concern WHO created and coordinates the Global Influenza Surveillance and Response System in order to provide necessary information for viral variants selection that will be part of vaccine annual composition, since that, vaccination is one of the most effective measures for influenza prevention and its complications. In addition, the network is a rapid surveillance of emerging influenza virus identifications with potential to cause epidemic or pandemic situations. The surveillance isenable due to laboratory tests results which are important tools for public health, with essential role for circulating viruses containment and prevention. The aim of this study was to present information related to influenza virus and flu disease, how the diagnosis and monitoring are performed by global surveillance networks at post pandemic time and, also,the new challenges facing.

Peripheral T-cell lymphoma at the injection site of influenza vaccination.

Pseudolymphomas or B-cell lymphoma at the vaccination site have been reported by several authors. However, onset of cutaneous T-cell lymphoma with cytotoxic features is a rare complication of vaccination. We report a 27-year-old man who developed a nodule and ulcer that arose at the site of injection of influenza vaccine. The neoplastic cells reacted positively for CD56, CD3, CD2, perforin, and granzyme B, but negatively for CD4, CD8, CD10, CD19, CD30, CD34, CD79, and betaF1. Molecular studies showed T-cell receptor γ (TCR-γ) chain monoclonal rearrangement. A diagnosis of peripheral T-cell lymphoma, not otherwise specified (NOS) was established. The patient had high fever, progressive liver dysfunction and a rapid fatal evolution.

Boletín de la Cooperación Técnica, enero-abril 2014

[Introducción]. Presentar a las autoridades nacionales de salud los proyectos actuales del programa de influenza (OPS, CDC, división de influenza y acuerdo cooperativos) para solicitar la participación de Cuba en la caracterización de la estacionalidad de la influenza y estimación de la carga de enfermedad debida al virus en Centro-América y el Caribe; y en la evaluación de la efectividad y del impacto de la vacuna contra influenza estacional en el marco de la Red para Evaluación de la Efectividad de la Vacuna en Latino América y el Caribe-influenza, (REVELAC-i)

Autoantibodies in immune-mediated neuropathies.

PURPOSE OF REVIEW: Over the past 25 years, many autoantibodies directed against peripheral nerve glycan and protein antigens have been described. Principally through this area of research, significant advances have been achieved in the understanding of the pathophysiology of inflammatory neuropathies. More evidence constantly continues to emerge supporting the role of antibodies in pathogenesis. This review reports the recent studies highlighting the complex association between autoantibodies directed against various peripheral nerve antigens and immune polyneuropathies. RECENT FINDINGS: The discovery of serum antibodies directed against ganglioside and glycolipid complexes has generated huge interest in this area of research. The expectation that nodal proteins are important targets continues to be pursued in line with the improvements in detection methodology. Basic studies continue to support a direct role for autoantibodies in neuropathy pathogenesis. SUMMARY: Discovery of new target epitopes has not only raised hopes for further improvement in our understanding of pathophysiology and availability of new diagnostic markers, but also for future targeted therapies. Further studies are required to elucidate the precise pathological and clinical significance of these new antibodies.

In vitro host range, multiplication and virion forms of recombinant viruses obtained from co-infection in vitro with a vaccinia-vectored influenza vaccine and a naturally occurring cowpox virus isolate.

BACKGROUND: Poxvirus-vectored vaccines against infectious diseases and cancer are currently under development. We hypothesized that the extensive use of poxvirus-vectored vaccine in future might result in co-infection and recombination between the vaccine virus and naturally occurring poxviruses, resulting in hybrid viruses with unpredictable characteristics. Previously, we confirmed that co-infecting in vitro a Modified vaccinia virus Ankara (MVA) strain engineered to express influenza virus haemagglutinin (HA) and nucleoprotein (NP) genes with a naturally occurring cowpox virus (CPXV-NOH1) resulted in recombinant progeny viruses (H Hansen, MI Okeke, Ø Nilssen, T Traavik, Vaccine 23: 499-506, 2004). In this study we analyzed the biological properties of parental and progeny hybrid viruses. RESULTS: Five CPXV/MVA progeny viruses were isolated based on plaque phenotype and the expression of influenza virus HA protein. Progeny hybrid viruses displayed in vitro cell line tropism of CPXV-NOH1, but not that of MVA. The HA transgene or its expression was lost on serial passage of transgenic viruses and the speed at which HA expression was lost varied with cell lines. The HA transgene in the progeny viruses or its expression was stable in African Green Monkey derived Vero cells but became unstable in rat derived IEC-6 cells. Hybrid viruses lacking the HA transgene have higher levels of virus multiplication in mammalian cell lines and produced more enveloped virions than the transgene positive progenitor virus strain. Analysis of the subcellular localization of the transgenic HA protein showed that neither virus strain nor cell line have effect on the subcellular targets of the HA protein. The influenza virus HA protein was targeted to enveloped virions, plasma membrane, Golgi apparatus and cytoplasmic vesicles. CONCLUSION: Our results suggest that homologous recombination between poxvirus-vectored vaccine and naturally circulating poxviruses, genetic instability of the transgene, accumulation of non-transgene expressing vectors or hybrid virus progenies, as well as cell line/type specific selection against the transgene are potential complications that may result if poxvirus vectored vaccines are extensively used in animals and man.

Erythema multiforme following vaccination in an infant.

Erythema multiforme is a cutaneous reaction pattern precipitated by varied agents, notably herpes simplex and drugs. It predominantly occurs in adolescents and young adults but may be seen at other ages also. While vaccination is rarely a precipitating factor for erythema multiforme, it may occasionally be seen in infants and children. We report here a case of a two month-old infant with lesions of erythema multiforme minor appearing after two weeks following vaccination for DPT, Hepatitis B and influenza.